Pre-Cancer: Molecular Basis of Cancer Flashcards Preview

Mini II > Pre-Cancer: Molecular Basis of Cancer > Flashcards

Flashcards in Pre-Cancer: Molecular Basis of Cancer Deck (93):
1

what is the pre-cancerous condition of the stomach that leads to gastric adenocarcinoma?

Atrophic Gastritis of pernicious anemia

2

what pre-cancerous condition leads to melanoma in the skin?

dysplastic nevus

3

Barrett esophagus leads to?

Adenocarcinoma of esophagus

4

H. pylori infection can lead to?

Adenocarcinoma of stomach
MALT lymphoma (MALToma)

5

Chronic ulcerative colitis can lead to?

Adenocarcinoma of colon

6

Hep B, Hep C, cirrhosis can all lead to?

Hepatocellular carcinoma

7

Atypical ductal hyperplasia can lead to?

Adenocarcinoma of boob

8

Lichen sclerosis can lead to?

Squamous cell carcinoma of Vulva

9

Chronic cystitis can lead to?

Urothelial carcinoma of urinary bladder

10

RB1- predisposition for?

Retinoblastoma

11

p53- predisposition for?

Li-Fraumeni syndrome (multiple tumors)

12

APC- predisposition for?

Familial adenomatous polyposis

13

NF1, NF2- predisposition for?

Neurofibromatosis 1
Neurofibromatosis 2 (bilateral Schwannoma of acoustic nerve)

14

BRCA1, BRCA2- predisposition for?

Breast cancer, Ovarian cancer

15

MEN1, RET- predisposition for?

Multiple endocrine neoplasia 1 and 2

16

p16INK4A (CDKN2A)- predisposition for?

Melanoma

17

MSH2, MLH1, MSH6- predisposition for?

Hereditary non-polyposis colon cancer

18

Retinoblastoma

what is the two hit theory?
What is the MOA behind Retinoblastoma?
What are the clinical signs?
Predisposition for ___ in adolescents?

Loss of RB tumor suppressor gene on chromo 13. It is a malignancy of eye in children

"two-hit theory"
- one gene inactivated in germ cells, the other after birth.

- White pupillary reflex & visual loss

- Predisposition for Osteosarcoma in adolescence

19

Familial Adenomatous Polyposis (FAP). Leads to development of what?

Inactivation of APC tumor suppressor gene

Development of Colorectal carcinoma from malignant transformation of polyps by age 30

20

Multiple Endocrine Neoplasia

MEN II --> mutation of rET protooncogene

familial occurence is combination:
1. medullary thyroid carcinoma
2. bilateral pheochromocytoma
3. hyperparathyroidism due to hyperplasia or tumor

21

Herditary Non-polyposis Colorectal Cancer (HNPCC)

-familial clustering of cancers at several sites
- colon cancers at young age (often R sided)
-DNA mismatch repair (MSH2 and MLH1 and MSH6)

"Cluster of genes, cluster of cancer"

22

Xeroderma pigmentosum

Mutated Nucleotide Excision Repair (NER) enzymes.

Defect in DNA repair of UV damaged skin

Predisposition to multiple skin cancers- Basal cell carcinoma, squamous cell carcinoma, malignant melanoma

excessive photosensitivity and 2000x increase in skin cancers

23

Ataxia-telangiectasia

Mutated ATM gene which usually repairs DNA damaged by ionizing radiation

Predisposition to lymphoma, leukemia, breast cancer

24

Bloom's syndrome

Mutated BLM gene. DNA helicase family

Predisposition to lymphoma, leukemia

25

Fanconi's anemia

Mutated FAC gene

Predisposition to lymphoma, leukemia and bone marrow aplasia

26

Breast/ovarian cancer

Inactivated BRCA1, BRCA2 genes

27

Familial melanoma

Mutated p16INK4A gene

28

Overexpression of PDGFB gene or TGF-alpha

Astrocytoma

29

Overexpression of HST1 gene

Osteosarcoma

30

Amplification of FGF3 gene

Stomach
Bladder
Breast
Melanoma

31

Overexpression of HGF

Hepatocellular carcinoma
Thyroid cancer

32

amplification of ERBB2 (HER) causes ____ cancer

Breast carcinoma

33

Point mutation of RET causes ________ cancers



Multiple endocrine neoplasia 2A and B
and
Familial medullary thyroid carcinomas

34

Translocation on ABL gene

CHRONIC myelogenous leukemia

35

Point mutation at ABL gene

ACUTE lymphoblastic leukemia

36

Point mutation at BRAF gene

Melanoma

37

What causes burkitt lymphoma?

translocaiton on MYC

38

What causes neuroblastoma?

Amplification of N-MYC

39

Point mutation in ____ gene is found in 15-20% of all cancers

RAS

40

t(9;22)

Chronic myeloid leukemia (CML)

ABL, BCR genes- forms Philadelphia chromosome

41

t(8;14)

Burkitt lymphoma

Overexpression of c-MYC, IGH

(overexpression of proto-oncogene M). You get "starry sky".

42

t(14;18)

Follicular lymphoma

Overexpression of BCL2 (anti-apoptosis). results in immortality of B-lymphocytes

43

t(15;17)

Acute myeloid leukemia

PML and RARA genes

44

t(11;14)

Mantle cell lymphoma
Cyclin D1 and IGH genes

generalized non-tender lymphadenopathy in elderly male patient

45

t(11;22)

Ewing Sarcoma

FLI1 and EWSR1 genes
"X-ray tibia, onion-skin pattern, round-dark blue nuclei"

46

Presence of _____ in >90% of tumors

Telomerase

47

what skin condition leads to squamous cell carcinoma of skin?

actinic (solar) keratosis

48

what precancerous condition in the oral cavity leads to oral squamous cell carcinoma?

oral leukoplakia

49

what cancer is associated with the bronchial mucosa?

squamous cell carcinoma of lung. The precursor lesion is squamous metaplasia --> dysplasia

50

tubular/villous adenoma can lead to what cancer

adenocarcinoma of colon

51

endometrial hyperplasia can lead to?

adenocarcinoma of endometrium

52

a serous borderline tumor of ovary can lead to what?

serous papillary cystadenocarcinoma of ovary

53

inherited AR syndromes of defective DNA repair (4)

xeroderma pigmentosa
ataxia telangiectasia
bloom syndrome
fanconi anemia

54

familial cancers (2)

breast and ovarian

55

what are the 5 categories of oncogenes?

1. GF (ex: PDGF, FGF)
2. GF receptors (ex: EGF receptor)
3. Signal transducers (ex: RAS, B-catenin)
4. Cell cycle regulators (Cyclin D, CDK4, Cyclin E)
5. transcription factor (i.e. C-MYC or N-MYC)

56

Point mutaiton of K-RAS causes ____



colon, lung and pancreatic cancers

57

point mutation of H-RAS causes ____



bladder and kidney tumors

58

Point mutaiton of N-RAS causes ____



melanomas, hematologic malignancies

59

List 4 growth factors?

PDGF-beta
FGF
TGF-alpha
HGF

60

List 4 GF receptors?

ERBB2/HER
RET
PDGFRB
KIT

61

List 3 signal transducers?

RAS (K, H, and N)
ABL (non-receptor tyrosine kinase)
BRAF (RAS)

62

List 2 transcriptional activators?

MYC
n-MYC

63

List 2 cell cycle regulators?

CCNDA1
CDK4

64

what proto-oncogene causes mantle cell lymphoma?

CCND1

65

what proto-oncogene causes melanoma?

CDK4

66

point mutation in BRAF leads to ?

melanoma

67

point mutation in RET leads to?

MEN 2a and B familial medullary thyroid carcinoma

68

point mutation in KRAS leads to? (kristen rat sarcoma viral oncogene homolog)

pancreas and colon cancer

69

RAS proto-oncogene MOA

When RAS is bound to GDP it is "OFF"

GF binds, GDP gets removed --> RAS-GTP = "active" and can send message to nucleus.

"GAP" GTPase associated protein helps shut down active form of RAS by converting back to inactivated RAS-GDP (cuts away phosphate).

in a mutant RAS, phosphate cannot be removed from active RAS by GAP.

70

APC

function? associated cancer?

prevents nuclear transcription. Tumore supressor gene.

familial polyposis coli (inherited mutation)
and
sporadic colon cancer (somatic mutation)

71

BRAC1 and BRCA2

function? associated cancer?

regulated DNA repair

breast and ovarian cancer

72

RB

function? associated cancer?

inhibits G1 to S

retinoblastoma and osteogenic sarcoma

73

NF-1

function? associated cancer?

encodes neurobromin 1 = GTPase that acts as negative regulator of RAS

neurofibromatosis type I

74

NF-2

function? associated cancer?

cytoskeleton protein involved in contact inhibition

Neurofibromatosis type II- bilateral Schawannoma of acoustic nerve (hearing disturbances)

75

P53

function? associated cancer?

inhibits G1 to S, repairs DNA, activates BAX (initiates apoptosis)

50% of all cancers
Li-Fraumeni
Oncogenesis in HPV

76

VHL

function? associated cancer?

ubiquitin-ligase complex and hypoxia inducible factor 1a (HIF1a)

Von Hippel Lindau disease, hereditary renal cell carcinoma, pheochromocytoma and renal cysts

77

PTEN

function? associated cancer?

regulates nuclear transcription

cowden syndrome, CARCINOMA OF ENDOMETRIUM, breast and thyroid

78

WT1

function? associated cancer?

Transcriptional activator of genes invovled in normal development of genitorurinary tissue

Wilms' tumor

79

what is the main gene involved in neuroblastoma?

N-MYC

80

What is Trastumuzab (Herceptin) associated with?

it is monoclonoal Ab against Her-2/Neu for Breast cancer

81

What is the MOA of APC?

normal function: down-regulates Beta-Catenin and prevents its accumulation.

when APC is lost: B- catenin increases and it travels to nucleus where ther eis continuas WNT signaling causing FAP non-familial colorectal Cancer and sporadic adenoma

82

What is E-Cadherin?

it is a cell adhesion molecule that keeps eepithelial cells attached to each other.

for tumor to spread locally and metastasize it must detach.

associated with AD familial gastric carcinoma and sporadic carcinomas.

83

What is CDKN2A? (cycklin dependent kinase inhibitor 2A?

encodes 2 tumor suppressor genes (P16INK4a and ARF)

associated with AD famililal melanoma

84

what is RB?

tumor suppressor that inhibits movement from G1 to S phase

85

What is RB associated with?

retinoblastoma, osteogenic sarcoma, soft tissue carcinoma

86

What is the MOA of RB?

RB "holds" E2F = "hypophosphorylated state" and cell replication is preventated (i.e. cell can't move from G1 to S).

RB gets phosphorylated by cyclin D/CDK4 which then releases E2F.

If RB gets mutated, E2F is free and cells can easily go from G1 to S and cause tumor.

87

What is Knudson's 2 hit hypothesis

Both alleles of RB locus must be inactivaed.

40% of retinoblastoma are familial
1st hit = all somatic cells of body (one defective copy is inherited from affected parent and other copy is normal)
2nd hit =retinal cells (somatic mutation --> loss of normal RB gene --> retinoblastoma)

60% cases sporadic
cells homozygouse for mutant RB --> cancer
Recessive --> heterozygous cells are normal

88

P53 MOA

inhibits G1 to S, repairs DNA and activates BAX.

89

how many copies of the P53 must be knocked out for tumor formation?

both

90

Li-Fraumeni syndrome

increased risk of carcinomas/sarcomas-- inherited p53 mutation

91

what causes oncogenesis in HPV?

viral proteins E6 and E7
bind to inhibit RB and p53

92

MOA of BCL-2?

stabilizes mitochondrial membrane so cytochome C can't be released. If it is inhibited, cytochrome C can leak out of mitochondria and activate apoptosis.

Translocation 14:18 overexpresses BCL-2 which prevents apoptosis of B cells and prevents apoptosis of B cells (B cell lymphoma) follicular lymphoma.

93

Telomerase

limitless replicative potential. Normal somatic cells have 60 to 70 doublings.

telomerase is in over 90% tumors